Research Papers:

Stress and stem cells: adult Muse cells tolerate extensive genotoxic stimuli better than mesenchymal stromal cells

Nicola Alessio, Tiziana Squillaro, Servet Özcan, Giovanni Di Bernardo, Massimo Venditti, Mariarosa Melone, Gianfranco Peluso and Umberto Galderisi _

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Oncotarget. 2018; 9:19328-19341. https://doi.org/10.18632/oncotarget.25039

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Nicola Alessio2, Tiziana Squillaro2, Servet Özcan1, Giovanni Di Bernardo2, Massimo Venditti2, Mariarosa Melone3,5, Gianfranco Peluso4 and Umberto Galderisi1,2,3

1Genome and Stem Cell Center (GENKOK), Erciyes University, Kayseri, Turkey

2Department of Experimental Medicine, Campania University “Luigi Vanvitelli,” Naples, Italy

3Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Temple University, Philadelphia, PA, USA

4Institute of Bioscience and Bioresources, CNR, Naples, Italy

52nd Division of Neurology, Center for Rare Diseases & InterUniversity Center for Research in Neurosciences, Department of Medical, Surgical, Neurological, Metabolic Sciences, and Aging, University of Campania “Luigi Vanvitelli”, Napoli, Italy

Correspondence to:

Umberto Galderisi, email: [email protected]

Keywords: mesenchymal stem cells; senescence; apoptosis

Received: January 12, 2018     Accepted: March 17, 2018     Published: April 10, 2018


Mesenchymal stromal cells (MSCs) are not a homogenous population but comprehend several cell types, such as stem cells, progenitor cells, fibroblasts, and other types of cells. Among these is a population of pluripotent stem cells, which represent around 1–3% of MSCs. These cells, named multilineage-differentiating stress enduring (Muse) cells, are stress-tolerant cells.

Stem cells may undergo several rounds of intrinsic and extrinsic stresses due to their long life and must have a robust and effective DNA damage checkpoint and DNA repair mechanism, which, following a genotoxic episode, promote the complete recovery of cells rather than triggering senescence and/or apoptosis.

We evaluated how Muse cells can cope with DNA damaging stress in comparison with MSCs. We found that Muse cells were resistant to chemical and physical genotoxic stresses better than non-Muse cells. Indeed, the level of senescence and apoptosis was lower in Muse cells. Our results proved that the DNA damage repair system (DDR) was properly activated following injury in Muse cells. While in non-Muse cells some anomalies may have occurred because, in some cases, the activation of the DDR persisted by 48 hr post damage, in others no activation took place.

In Muse cells, the non-homologous end joining (NHEJ) enzymatic activity increases compared to other cells, while single-strand repair activity (NER, BER) does not. In conclusion, the high ability of Muse cells to cope with genotoxic stress is related to their quick and efficient sensing of DNA damage and activation of DNA repair systems.

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